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81.
82.
Distinction between binding and endocytosis of human asialo-transferrin by the rat liver 总被引:4,自引:2,他引:2 下载免费PDF全文
Erwin Regoeczi Patricia Taylor Mark W. C. Hatton Kwong-Loi Wong Alex Koj 《The Biochemical journal》1978,174(1):171-178
The ability of the rat liver to bind and endocytose human asialo-transferrin was investigated in vivo. Asialo-transferrin was separated from incompletely desialylated transferrin and neuraminidase by chromatography before being labelled with 125I. Plasma radioactivity curves and hepatic radioactivity contents measured over a 1270-fold dose range led to the following observation. At the lowest dose (0.4μg/100g body wt.), the distribution of asialo-transferrin between plasma and liver resembled a reversible reaction reaching equilibrium in approx. 20min. After 35min, 93% of the dose was recovered with the plasma and liver as protein-bound radioactivity. Most of the asialo-transferrin associated with the liver could be displaced by asialo-orosomucoid, indicating that binding of asialo-transferrin to the galactose-specific lectin on the plasma membrane of hepatocytes was not followed by a signal for endocytosis. A range of doses, up to an average of 509.2μg of asialo-transferrin per 100g body wt., resulted in progressive increments in asialo-transferrin catabolism, as evidenced by lower dose recoveries and increased concentrations of non-protein-associated radioactivity in the liver and plasma volume. These observations indicate that binding and endocytosis of human asialo-transferrin by the rat hepatocyte are distinct phenomena. Individual asialo-transferrin molecules, although readily bound by the hepatic lectin, lack either the quantity or spacing of terminal galactose residues necessary for triggering endocytosis. Although endocytosis is induced by several asialo-transferrin molecules acting synergistically, preliminary experiments with asialo-glycopeptides and other substances have so far failed to provide further insight into the chemical basis of the signal for endocytosis. 相似文献
83.
Three types of human asialo-transferrin and their interactions with the rat liver 总被引:7,自引:2,他引:5 下载免费PDF全文
Erwin Regoeczi Patricia Taylor Maria T. Debanne Leopold M?rz Mark W. C. Hatton 《The Biochemical journal》1979,184(2):399-407
Three types of asialo-transferrin were obtained from immunologically pure human transferrin by chromatography on DEAE-cellulose, followed by desialylation and affinity chromatography on a column of the immobilized asialo-glycoprotein-binding hepatic lectin from rabbit liver. Of the asialo-transferrins, type 1 was derived from the principal DEAE-cellulose chromatographic component of transferrin, i.e. the one that contains two biantennary glycans. The two other asialo-transferrins (types 2 and 3) were derived from a minor DEAE-chromatographic transferrin component, which is assumed to possess one biantennary and one triantennary glycan. The three asialo-transferrin types were indistinguishable by electrophoretic mobility, but they were readily distinguished on the basis of their binding strengths to the hepatic lectin in intact rats. Glycan structures responsible for the difference in binding strengths between asialo-transferrin types 2 and 3 are not known. Metabolic studies in rats showed that none of the individual asialo-transferrin types was capable of generating a signal for endocytosis at low doses (<1mug/100g body wt.) and, consequently, most of the injected protein was recoverable with the plasma and the liver 35min after injection. However, endocytosis and catabolism of each asialo-transferrin type was readily induced by injecting a larger dose (50-250mug/100g body wt.) of unlabelled asialo-transferrin of the same type or of a different type a short interval after the labelled dose. These findings support the view that the dose-dependent uptake of human asialo-transferrin by the hepatocyte, as established in an earlier study with asialo-transferrin made from whole transferrin [Regoeczi, Taylor, Hatton, Wong & Koj (1978) Biochem. J.174, 171-178], also holds for these asialo-transferrin subfractions. Furthermore, the present studies indicate that asialo-transferrins of different carbohydrate compositions are capable of synergistically promoting endocytosis of each other. 相似文献
84.
Human, rabbit and bovine thrombins are shown to possess marked affinities for Sepharose-lysine. Using either Xa-activated crude prothrombins (human, rabbit) or a commercial thrombin sample (bovine), the enzyme was isolated in a single chromatographic step by the affinity medium and preparations of high specific activity were obtained. The relevance of bound-lysine for the affinity of the thrombins was studied using other Sepharose conjugates with structures related to Sepharose-lysine. Using freshly activated prothrombins it was found that human and rabbit thrombin uptake required a conjugate with a spacer chain containing a minimum of four carbon atoms in length which supported a terminal amino group. As the thrombin activity aged, affinity for the terminal amino group decreased but the hydrophobic spacer chain became essential for enzyme binding. The active centre of thrombin was not involved in binding to Sepharose-lysine. 相似文献
85.
The behaviour of desialylated human and chicken acid alpha1-glycoproteins is reported in chickens. Although desialylation resulted in accelerated disappearance rates from the plasma of both proteins, nevertheless the asialoproteins were eliminated much more slowly than expected on the basis of earlier observations in mammals. Analysis of tissue radioactivities, including kidney, liver, lung and spleen, failed to demonstrate any accumulation of the labeled asialoproteins in the liver, which is contrary to the situation in mammals. The main pathway for the elimination of desialylated human acid alpha1-glycoprotein in the chicken is via the kidney (tubular catabolism and/or urinary excretion). The clearance of desialylated chicken acid alpha1-glycoprotein is more complex as it involves the kidney as well as the reticuloendothelial system. These findings indicate that, unlike mammals, chickens do not possess a hepatic plasma membrane receptor for asialoglycoproteins. This raises the possibility that the presence or absence of this specific receptor may constitute a fundamental biological difference between mammals and birds. 相似文献
86.
Hatton LS Eloranta JJ Figueiredo LM Takagaki Y Manley JL O'Hare K 《Nucleic acids research》2000,28(2):520-526
During mRNA 3′ end formation, cleavage stimulation factor (CstF) binds to a GU-rich sequence downstream from the polyadenylation site and helps to stabilise the binding of cleavage-polyadenylation specificity factor (CPSF) to the upstream polyadenylation sequence (AAUAAA). The 64 kDa subunit of CstF (CstF-64) contains an RNA binding domain and is responsible for the RNA binding activity of CstF. It interacts with CstF-77, which in turn interacts with CPSF. The Drosophila suppressor of forked gene encodes a homologue of CstF-77, and mutations in it affect mRNA 3′ end formation in vivo. A Drosophila homologue for CstF-64 has now been isolated, both through homology with the human protein and through protein–protein interaction in yeast with the suppressor of forked gene product. Alignment of CstF-64 homologues shows that the proteins have a conserved N-terminal 200 amino acids, the first half of which is the RNA binding domain with the second half likely to contain the CstF-77 interaction domain; a central region variable in length and rich in glycine, proline and glutamine residues and containing an unusual degenerate repeat motif; and then a conserved C-terminal 50 amino acids. In Drosophila, the CstF-64 gene has a single 63 bp intron, is transcribed throughout development and probably corresponds to l(3)91Cd. 相似文献
87.
88.
Antibodies to citrullinated proteins and differences in clinical progression of rheumatoid arthritis
van der Helm-van Mil AH Verpoort KN Breedveld FC Toes RE Huizinga TW 《Arthritis research & therapy》2005,7(5):R949-R958
Antibodies to citrullinated proteins (anti-cyclic-citrullinated peptide [anti-CCP] antibodies) are highly specific for rheumatoid
arthritis (RA) and precede the onset of disease symptoms, indicating a pathogenetic role for these antibodies in RA. We recently
showed that distinct genetic risk factors are associated with either anti-CCP-positive disease or anti-CCP-negative disease.
These data are important as they indicate that distinct pathogenic mechanisms are underlying anti-CCP-positive disease or
anti-CCP-negative disease. Likewise, these observations raise the question of whether anti-CCP-positive RA and anti-CCP-negative
RA are clinically different disease entities. We therefore investigated whether RA patients with anti-CCP antibodies have
a different clinical presentation and disease course compared with patients without these autoantibodies. In a cohort of 454
incident patients with RA, 228 patients were anti-CCP-positive and 226 patients were anti-CCP-negative. The early symptoms,
tender and swollen joint count, and C-reactive protein level at inclusion, as well as the swollen joint count and radiological
destruction during 4 years of follow-up, were compared for the two groups. There were no differences in morning stiffness,
type, location and distribution of early symptoms, patients' rated disease activity and C-reactive protein at inclusion between
RA patients with and without anti-CCP antibodies. The mean tender and swollen joint count for the different joints at inclusion
was similar. At follow-up, patients with anti-CCP antibodies had more swollen joints and more severe radiological destruction.
Nevertheless, the distribution of affected joints, for swelling, bone erosions and joint space narrowing, was similar. In
conclusion, the phenotype of RA patients with or without anti-CCP antibodies is similar with respect to clinical presentation
but differs with respect to disease course. 相似文献
89.
90.